Recent studies in the PI's laboratory have provided evidence that FSH secretion can be characterized by episodic and basal secretion modes. The basal component of FSH secretion appears to be the dominant mode. While basal FSH secretion is not under acute control of GnRH, the level of basal FSH secretion can be altered by changes in activin, inhibin, and follistatin tone. These pituitary regulatory proteins appear to be synthesized and act probably via paracrine/autocrine modes to modulate basal FSH secretion. When the hypothalamus is disconnected from the pituitary, basal FSH secretion is significantly reduced which suggests that hypothalamic input is a necessary component in setting basal FSH tone. The longterm goal of this proposal is to investigate the mechanisms that regulate the release of basal FSH secretion. The overall hypothesis to be tested is that the level of FSH secretion during any physiologic state is primarily determined by the bioavailability of activin, a potent stimulator of FSH biosynthesis and secretion. Activin bioavailablity is in turn, determined by the prevailing tone of inhibin and follistatin and the available pituitary activin receptors. Integrative studies are proposed to dissect the complex functional overlaps among these FSH regulatory proteins at the pituitary level. Techniques such as hypophyseal-portal sampling, hypothalamo-pituitary disconnect techniques, in situ hybridization, antisense technology, and long-term pituitary cell perifusion studies will be utilized to determine how the hypothalamus and pituitary interact in controlling the mechanisms which govern basal FSH release.